The level of Na-pump activity has been implicated in mechanisms which could contribute to human obesity. Na, K-ATPase activity is reduced in intact red cells and isolated crythrocyte membranes from obese Pima Indian subjects. Isolated adipocytes had diminished insulin stimulation of Na,K-ATPase activity in obese compared to lean subjects. In addition, caloric restriction in vivo which has been shown to reduce metabolic rate, resulted in a reduced basal and maximal insulin stimulated Na,L-ATPase activity in isolated fat cells. No differences were observed, however, in the basal or insulin stimulated Na-pump activity for cultured diploid fibroblasts. Thus, diminished KaKAA may not be an inherent defect, but may be a manifestation of the insulin resistance state which contributes to the development of obesity via decreased cellular thermogenesis.